Abstract

Insulin signaling in the hypothalamus regulates food intake and hepatic glucose production in rodents. Although it is known that insulin also activates insulin receptor in the dorsal vagal complex (DVC) to lower glucose production through an Erk1/2-dependent and PI3K-independent pathway, it is unknown whether DVC insulin action regulates food intake. We here report that a single acute infusion of insulin into the DVC decreased food intake in healthy male rats. Chemical and molecular inhibition of Erk1/2 signaling in the DVC negated the acute anorectic effect of insulin in healthy rats, while DVC insulin acute infusion failed to lower food intake in high-fat fed rats. Finally, molecular disruption of Erk1/2 signaling in the DVC of healthy rats per se increased food intake and induced obesity over a period of two weeks, while a daily repeated acute DVC insulin infusion for 12 days conversely decreased food intake and body weight in healthy rats. In summary, insulin activates Erk1/2 signaling in the DVC to regulate energy balance.